Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?”
Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron d...
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oai:doaj.org-article:9a55450d837e456f908ac29ee726b0582021-11-25T17:58:07ZHypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?”10.3390/ijms2222125901422-00671661-6596https://doaj.org/article/9a55450d837e456f908ac29ee726b0582021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12590https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients’ dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.Giuseppina CruglianoRaffaele SerraNicola IelapiYuri BattagliaGiuseppe CoppolinoDavide BolignanoUmberto Marcello BracaleAntonio PisaniTeresa FagaAshour MichaelMichele ProvenzanoMichele AndreucciMDPI AGarticlechronic kidney diseaseanemiaerythropoietintreatmentrenal diseaserenal failureBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12590, p 12590 (2021) |
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| collection |
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| language |
EN |
| topic |
chronic kidney disease anemia erythropoietin treatment renal disease renal failure Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
chronic kidney disease anemia erythropoietin treatment renal disease renal failure Biology (General) QH301-705.5 Chemistry QD1-999 Giuseppina Crugliano Raffaele Serra Nicola Ielapi Yuri Battaglia Giuseppe Coppolino Davide Bolignano Umberto Marcello Bracale Antonio Pisani Teresa Faga Ashour Michael Michele Provenzano Michele Andreucci Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?” |
| description |
Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients’ dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action. |
| format |
article |
| author |
Giuseppina Crugliano Raffaele Serra Nicola Ielapi Yuri Battaglia Giuseppe Coppolino Davide Bolignano Umberto Marcello Bracale Antonio Pisani Teresa Faga Ashour Michael Michele Provenzano Michele Andreucci |
| author_facet |
Giuseppina Crugliano Raffaele Serra Nicola Ielapi Yuri Battaglia Giuseppe Coppolino Davide Bolignano Umberto Marcello Bracale Antonio Pisani Teresa Faga Ashour Michael Michele Provenzano Michele Andreucci |
| author_sort |
Giuseppina Crugliano |
| title |
Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?” |
| title_short |
Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?” |
| title_full |
Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?” |
| title_fullStr |
Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?” |
| title_full_unstemmed |
Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?” |
| title_sort |
hypoxia-inducible factor stabilizers in end stage kidney disease: “can the promise be kept?” |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/9a55450d837e456f908ac29ee726b058 |
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